We propose to investigate the immune responses of spinal fluid lymphocytes in patients with multiple sclerosis. We plan to: a. determine the antigens to which these cells respond; b. determine the regulatory responses evoked by these cells; c. define the idiotypes of their antigen receptors; and d. use these lymphocytes to characterize differences in cells from monozygotic twins discordant for MS. To accomplish this spinal fluid lymphocytes from patients and control individuals will be stimulated with autologous, allogeneic and soluble brain and viral antigens and their responses to these antigens analyzed at the clonal level. Since MS may be an autoimmune disease, characterization of the responses of immunocompetent cells in the central nervous system may help elucidate the etiology of this disease.